It is proposed to study the mechanism of iron mobilization in humans and to design and build a hemodialysis unit capable of removing iron from heavily transfused patients. Our research on natural mechanisms of iron mobilization centers about the iron storage protein, ferritin, and the iron transport protein, transferrin. Using two isotopes of iron, we will study the effects of chelating agents, redox reagents, pH, degree of iron saturation, and the presence of the protein, ceruloplasmin on the transfer of iron in both directions between transferrin and ferritin. The effect on the iron core of the heat treatment used in isolating ferritin will be assessed by studying the infrared and Raman spectra and iron mobilization from ferritin prepared with or without heating. The biological function of the two iron-binding sites of transferrin will be probed by labeling each with a different isotope of iron, making use of the different pH dependence of the two binding constants. After checking the validity of the labeling technique using electron spin resonance spectroscopy, the doubly labeled protein will be incubated with reticulocytes to test for a preferential uptake of one isotope of iron. We hope to design, construct and test a hemodialysis unit capable of removing iron from plasma. The principle involved is to remove iron from the circulating transferrin, using chelating agents at low pH. The process envisaged will probably require separation of the cells and plasma in a continuous flow centrifuge, removal of iron from the plasma at low pH, and restoration of the plasma to physiologically acceptible form. The proposed hemodialysis procedure will be especially useful in treating heavily transfused patients with aplastic anemia or thalassemia major.